A systematic review investigating at what proportion clinical images are shared in prospective randomized controlled trials involving patients with psoriasis and biological agents.

For many patients including those with psoriasis, scientific manuscripts comprising clinical outcomes including psoriasis area severity index (PASI) and/or physician global assessment (PGA) may be difficult to understand. However, most patients can relate to images at baseline and follow-up, particularly for dermatological diseases. This study aimed to assess the proportion of shared clinical images in psoriasis trials. A systematic review adhering to the PRISMA guidelines was performed. The review was limited to randomized controlled trials, and among these, only investigations involving biological agents for treatment of psoriasis were included. The Embase, MEDLINE and Scopus databases were searched for eligible studies published from inception to October 26, 2021. In total, 152 studies were included. When combining these, 62,871 patients were randomized. Overall, 203 images were shared depicting 60 patients in the manuscripts yielding an overall sharing rate of 0.1%. Patient images are seldom incorporated in clinical trial manuscripts which impairs interpretation for patients. Inclusion of image material would strengthen the patients' perspective and understanding on what treatment effects that can be expected. As such, this systematic review should be an invitation to the pharmaceutical industry, other sponsors, and editorial offices to improve easy transfer of information to patients using image data.

Chronic hand eczema: A prevalent disease in the general population associated with reduced quality of life and poor overall health measures.

BACKGROUND: The impact of hand eczema (HE) on Health-Related Quality of Life (HRQoL) has only been sparsely studied in a general population setting, and never by use of the disease specific Quality Of Life in Hand eczema Questionnaire (QOLHEQ). OBJECTIVES: To examine the HRQoL of unselected individuals with HE using the QOLHEQ. Further, to provide prevalence estimates of severe and chronic HE (CHE), and to contrast overall health related outcomes between individuals with and without HE. METHODS: In this nationwide, cross-sectional study a questionnaire covering questions on HE related outcomes, and overall health was sent to a random sample of 100 000 Danish adults via a secure digital mailbox, linked to their unique civil registration numbers. Data on demographic characteristics were retrieved from the civil registration system. Individuals reporting HE, further answered the QOLHEQ and other disease specific questions. RESULTS: The response rate was 42.7% (n = 42 691). Total estimates of lifetime, 1-year and point prevalences of HE were 24.4%, 13.3% and 5.8%. Of individuals reporting a 1-year prevalence, 35.1% reported moderate-severe disease and 82.6% CHE. Individuals with HE were more likely to report less good or poor overall health, and sick leave (any reason), compared to those without. In the 2176 (92.5%) with current HE who completed the QOLHEQ, median QOLHEQ scores corresponded to a moderate impairment of the symptoms and treatment and prevention domains and a slight impairment overall and for the emotions and functioning domains. Factors that were strongly associated with moderate to severe HRQoL impairment included severe, chronic and occupational HE as well as female sex. CONCLUSIONS: HE is highly prevalent, bears a considerable burden on society and significantly affects the lives of impacted individuals. Our findings indicate a necessity for targeted prevention aimed at high-risk groups, and support and treatment for those most affected.

Contact allergy to metals in metalworkers: A systematic review and meta-analysis.

Occupational hand eczema is frequent in metalworkers. The contribution of metal allergies is poorly elucidated even though such exposures are common at the workplace. To estimate the prevalence of metal allergy to cobalt (Co), chromium (Cr) and nickel (Ni) in metalworkers and compare these to estimates from the European Surveillance System on Contact Allergies (ESSCA). Two authors independently searched PubMed for studies reporting on the prevalence of metal allergy in metalworkers. Proportion meta-analyses were performed to calculate the pooled proportions of metal allergy in metalworkers. In total, 29 studies (22 from Europe) were included yielding 5691 subjects for quantitative analysis. The pooled proportion (95% confidence interval) of Co, Cr and Ni in European metalworkers with dermatitis referred to patch test clinics was 8.2% (5.3%-11.7%), 8.0% (5.1%-11.4%), and 11.0% (7.3%-15.4%), respectively. The corresponding estimates for unselected metalworkers from workplace studies were 4.9% (2.4%-8.1%), 5.2% (1.0%-12.6%), and 7.6% (3.8%-12.6%), respectively. In comparison, the prevalence of metal allergy in 13 382 consecutive European males with dermatitis was 3.9% (3.6%-4.2%), 4.4% (4.1%-4.8%) and 6.7% (6.3%-7.0%) for Co, Cr and Ni, respectively. Data on sex, age, body piercings and atopic dermatitis in metalworkers with metal allergy was mostly lacking. Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA data, indicating a relationship to occupational exposures, however, confounders could not be accounted for.

Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review.

BACKGROUND: The evidence for adding small-molecule drugs to an ongoing biologic treatment is sparse, but combination therapies appear to be advantageous in appropriately selected patients with psoriasis. To our knowledge, efficacy and safety of combination therapy with apremilast and biologics has not previously been reviewed. MATERIALS AND METHODS: A literature search was performed on Medline (PubMed), Embase, Web of Science, and the Cochrane Library. Inclusion criteria were a diagnosis of psoriasis, age ≥ 18 years, concomitant treatment with apremilast and a specified biologic agent, and available safety and/or efficacy results. All papers written in English and published from database inception to August 2021 were included. No limit was set regarding study size. RESULTS: The literature search yielded 447 citations. Of these, 19 studies published from 2015 to 2020 were included in the review. All papers referred to retrospective studies, comprising case reports (n = 9), case series (n = 8), or cohort studies (n = 2). A total of 172 patients with psoriasis were identified. Clinical subtypes included plaque psoriasis (n = 164), palmoplantar pustulosis (n = 7), and acute pustular psoriasis (n = 1). The observation period ranged from 3 weeks to 24 months. Geographical origin of studies was North America (n = 11), Europe (n = 4), and Asia (n = 4). In general, apremilast-biologic combination therapy was reported to be safe; across papers, one serious adverse event was registered (hospitalization due to weight loss). Adverse events (AEs) were otherwise mostly mild and gastrointestinal. No differences in AEs were observed in studies comparing apremilast mono- and combination therapy. In several papers, sufficient information about AEs was not reported or could not be extracted. Clinical response to combination treatment was evaluated at various time points, and only few studies used validated scores. In the remaining papers, efficacy data were descriptive and/or in photographic form, or not available. In total, two patients discontinued therapy due to lack of efficacy. CONCLUSION: Evidence for combined treatment with apremilast and biologics is limited and restricted to retrospective studies of various quality. Based on available data, apremilast may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed.

Chromium and cobalt release from metallic earrings from the Danish market.

BACKGROUND: Chromium and cobalt are important skin sensitizers. It has, however, been difficult to identify causative exposures. Studies on nickel allergy have demonstrated piercing as critical for both sensitization and elicitation. It may be speculated that the same applies for chromium and cobalt. OBJECTIVE: To examine the content and release of chromium and cobalt from earrings randomly purchased in Denmark. METHODS: Three hundred four earrings were examined with x-ray fluorescence (XRF) spectrometry. Earrings with measured content of chromium or cobalt were spot tested with diphenylcarbazide spot test (n = 166) or Nitroso-R spot-test (n = 99), respectively. Chromium and cobalt release were quantified in a selected subsample (n = 100) with the artificial sweat test (EN 1811). RESULTS: Chromium was present in 54.6% (166/304) of earrings and cobalt was present in 72.0% (219/304),- measured by XRF. All chromium spot tests for chromium VI were negative. The cobalt spot test was positive for one component. Chromium release was found from 59/100 (median concentration = -0.06 µg/cm2 /week) and cobalt release from 29/100 (median concentration = -0.06 µg/cm2 /week) of earrings in tested subsample. CONCLUSION: Earrings for piercing release chromium and cobalt and may on a case basis be a source of chromium and cobalt allergy.

No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy.

BACKGROUND: In March 2014, the European Commission issued a new regulation restricting the content of hexavalent chromium (Cr) in leather to no more than 3 mg/kg. We previously performed a questionnaire study in January 2014 to characterize our patients with Cr contact allergy prior to regulatory intervention. OBJECTIVES: To assess whether clinical characteristics, self-reported sources of Cr exposure, and burden of disease changed in patients with Cr allergy over time. METHODS: A questionnaire study was performed among 172 adult dermatitis patients with Cr allergy and 587 age- and sex-matched dermatitis patients without Cr allergy. A questionnaire was sent to all dermatitis patients patch tested from 2003 to 2018 in August 2019. RESULTS: The overall response rate was 61.2% (759/1241). Patients with Cr allergy were still more commonly affected by current foot dermatitis (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.07-7.08) and hand dermatitis (OR 1.98, 95% CI 1.13-3.49) compared with controls diagnosed during 2013 to 2018. The proportion of patients with Cr allergy reporting dermatitis caused by leather exposure did not change during 2003 to 2012 vs 2013 to 2018 (71.0% vs 66.2%, P = .5). Furthermore, estimates on occupational performance and disease severity (eg, current dermatitis), number of anatomical locations with dermatitis, worst-case dermatitis, and effect on work were similar in patients with Cr allergy for 2003 to 2012 vs 2013 to 2018. CONCLUSION: No immediate sign of improvement was found in patients with Cr allergy concerning severity of disease and dermatitis from leather exposures 5 years after adoption of the regulation against hexavalent Cr in leather. The regulation may have to be revised for better protection of those already sensitized.

Aluminium contact allergy without vaccination granulomas: A systematic review and meta-analysis.

Aluminium contact allergy is mainly seen as granulomas following immunization with aluminium-adsorbed vaccines and contact allergy following epicutaneous exposure may be overlooked. To investigate the prevalence of aluminium allergy confirmed by patch testing, with no association with vaccination granulomas, and explore whether epicutaneous exposure to aluminium can contribute to allergic contact dermatitis. Two authors independently searched PubMed and MEDLINE (OVID) for case studies on contact allergy to aluminium proven by patch testing. Age-stratified meta-analyses to calculate the pooled prevalence were performed. Twenty-five studies describing a total of 73 cases were included in the review. Seven studies were suitable for meta-analyses. The prevalence of aluminium contact allergy was 5.61% (95% confidence interval [CI] 0.12%-11.08%) for children and 0.36% (95% CI 0.04%-0.67%) for adults. The studies described a variety of epicutaneous exposures, where metallic aluminium, topical medicaments, and deodorants were the main sources. Aluminium sensitization without a known exposure source was described in 10 of the 25 articles. The prevalence of aluminium contact allergy in the general public may be higher than expected and not solely related to vaccination granulomas. However, the clinical relevance is rare if not related to granulomas.

Metals in used and unused metalworking fluids: X-ray fluorescence spectrometry as a screening test.

BACKGROUND: Exposure to metalworking fluids (MWFs) is a well-known cause of occupational contact dermatitis. OBJECTIVES: We aimed to (1) determine the amount of nickel, chromium, and cobalt in large samples of used and unused MWFs collected from metalworking plants in Denmark, and (2) evaluate a handheld x-ray fluorescence (XRF) device as a screening instrument for metals in MWFs. METHODS: A handheld XRF device was used to screen for metals in MWFs. All samples were also analyzed for concentrations of nickel, chromium, and cobalt using graphite furnace atomic absorption spectroscopy (GFAAS). RESULTS: GFAAS analysis showed that 13 of 80 samples (16.3%) contained >1 mg/kg (ppm) nickel (range: 6.4-17.7 mg/kg), 3 of 80 (3.8%) contained >1 (range: 1.4-3.1) mg/kg chromium, and 1 of 80 (1.3%) contained 1.3 mg/kg cobalt. XRF-screening detected nickel in eight samples (range: 2.5-15.5 mg/kg), but only one sample with 3.0 (±0.5) mg/kg was found subsequently to contain 9.9 (0.02) mg/kg nickel by GFAAS. Although no chromium was found by XRF analysis, cobalt was found in two samples with 6 (±1.5) mg/kg and 5 (±1.5) mg/kg, subsequently found to contain 0.1 (±0.01) mg/kg and 0.08 (±0.01) mg/kg by GFAAS. Similar concentrations of nickel were found in used (N = 6, range: 6.4-17.7 mg/kg) and unused MWFs (N = 7, range: 9.1-17.3 mg/kg). CONCLUSION: Considerable levels of nickel, chromium, and cobalt were found in some used and unused MWFs indicating that these might represent a source of metal allergy. The XRF device is a poor screening test for these metals in MWFs.

Global Prevalence and Bidirectional Association Between Psoriasis and Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Epidemiological studies have established an association between psoriasis and inflammatory bowel disease [IBD], i.e. ulcerative colitis [UC] and Crohn's disease [CD], but results are inconsistent. The aim of this study was therefore to quantify the prevalences and association between IBD and psoriasis. METHODS: PubMed, Web of Science, and EMBASE were searched from database inception through April 2018 for studies reporting data on psoriasis among patients with IBD and vice versa. Meta-analysis was performed to estimate, respectively, the prevalences and association between IBD and psoriasis. Data extraction was according to the PRISMA guideline, and quality assessment was made using the Newcastle-Ottawa Scale. The main outcomes were the proportion of psoriasis patients with IBD and vice versa, as well as the association (odds ratio [OR]) of IBD in psoriasis and psoriasis in IBD, respectively. RESULTS: Based on quantitative analysis of 93 studies, the prevalence of psoriasis in CD and in UC was 3.6% (95% confidence interval [CI] 3.1%-4.6%) and 2.8% [95% CI 2.0%-3.8%] respectively. The prevalence of CD and UC was 0.7% [95% CI 0.2%-1.3%] and 0.5% [95% CI 0.3%-0.8%], respectively, among patients with psoriasis. Presence of CD or UC was significantly associated with psoriasis, with OR 2.0 [95% CI 1.4-2.9] and OR 1.5 [95% CI 1.2-2.0], respectively. Presence of psoriasis was significantly associated with CD: OR 2.2 [95% CI 1.6-3.1] and with UC: OR 1.6 [95% CI 1.3-2.0]. CONCLUSIONS: We found significant bidirectional associations between psoriasis and IBD, warranting increased awareness among clinicians in the diagnostic process, especially in children and adolescents with IBD. Last, this study showed an increased frequency of paradoxical psoriasis in patients treated with biologics.

The Association Between Season of Birth and Atopic Dermatitis in the Northern Hemisphere: A Systematic Review and Meta-Analysis.

BACKGROUND: Cold and dry climate negatively affects skin barrier functions. This could explain the higher incidence of atopic dermatitis (AD) in Northern countries distant from the equator, as well as the general worsening of AD in Northern European winter months. Although it has been suggested that fall and winter birth is associated with AD, this remains unknown. OBJECTIVES: To examine whether the prevalence of AD is associated with season of birth. METHODS: We conducted a systematic review and meta-analysis. Two reviewers independently searched 3 databases. Study quality was assessed using a Newcastle-Ottawa scale. Study heterogeneity was assessed with Cochrane Q and I2 statistics. Odds ratios with 95% CIs were calculated. Publication bias was assessed using funnel plots. RESULTS: The systematic review identified 23 relevant articles of which 9 articles were included in the meta-analysis. Among a total of 726,378 children aged 0 to 12 years, the overall pooled prevalence of AD was 12.9%. The pooled prevalence of AD was 15.4% (95% CI, 12.1%-19.1%), 14.9% (95% CI, 12.0%-18.1%), 12.7% (95% CI, 10.2%-15.4%), and 13.7% (95% CI, 10.8%-17.0%), among children born in the fall, winter, spring, and summer, respectively. AD was significantly associated with fall (odds ratio, 1.16; 95% CI, 1.06-1.28; P = .0018) and winter (odds ratio, 1.15; 95% CI, 1.04-1.27; P = .0076) birth compared with spring birth. CONCLUSIONS: Although a positive and significant association was observed between being born in fall and winter and developing AD on the Northern hemisphere, there is a need for additional and better-designed studies to understand the effect of seasonal changes on the risk of AD.

Causative exposures and temporal development of cobalt allergy in Denmark between 2002 and 2017.

BACKGROUND: Cobalt contact allergy is common, but clinical relevance is often difficult to determine. OBJECTIVES: To examine the aetiology, prevalence and clinical characteristics of cobalt-allergic patients who were patch tested between 2002 and 2017 at the Department of Dermatology and Allergy, Herlev-Gentofte Hospital. METHODS: Patch test data, along with patient characteristics and causative exposures, from all adult dermatitis patients seen and tested between 2002 and 2017 were analysed. Associations were tested with the χ 2 test and logistic regression. RESULTS: A total of 13 475 adults aged 18 to 99 years were patch tested. The overall prevalence of cobalt allergy and the prevalence of isolated cobalt allergy were 3.3% and 1.5%, respectively. The prevalence of isolated cobalt allergy decreased from 2.4% in 2006 to 2009 to 1.1% in 2014 to 2017 (Ptrend = 0.00003). Leather exposure as a relevant cause of allergic cobalt dermatitis increased from 3.7% in 2002 to 2009 to 8.3% in 2010 to 2017 (P = 0.04). The current clinical relevance of positive patch test reactions, that is, a positive reaction to cobalt combined with a history of current skin exposure to a source of cobalt, was 20.1%. CONCLUSIONS: We conclude that cobalt allergy is relatively common, but causative exposures are largely unknown, and the proportion of positive patch test reactions with clinical relevance is low. It is therefore currently unclear how we can better protect consumers and workers from cobalt exposure.

Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies.

BACKGROUND: Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported. OBJECTIVES: To assess the prevalence and incidence of PsA in patients with psoriasis. METHODS: Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis. RESULTS: A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI]) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (<18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years. LIMITATIONS: Between-study heterogeneity may have affected the estimates. CONCLUSIONS: We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported.

Temporal changes in chromium allergy in Denmark between 2002 and 2017.

BACKGROUND: In 2012, Danish authorities submitted a proposal to the European Chemical Agency restricting the content of hexavalent chromium to a maximum of 3 ppm in leather goods. Following its adoption, this proposal was implemented in 2015 as a directive in the EU. OBJECTIVES: To examine the temporal trend of chromium contact allergy in adult dermatitis patients patch tested between 2002 and 2017, and to determine clinical characteristics and causative exposures in these patients. METHODS: All adult dermatitis patients patch tested between 2002 and 2017 were included. Patch test data were reviewed retrospectively. Comparisons were performed with the χ 2 test and logistic regression analysis. RESULTS: A total of 13 379 adults aged 18 to 99 years were patch tested between 2002 and 2017. The overall prevalence of chromium allergy was 2.2%. An overall decreasing trend was found for the prevalence of chromium allergy (Ptrend = 0.00002). Specifically, a significant difference was found for the study periods 2010 to 2013 (Ptrend = 0.002) and 2014 to 2017 (Ptrend < 0.0001) as compared with 2002 to 2005. Leather remained the most important single cause of allergic contact dermatitis caused by chromium. The proportion of clinically relevant leather exposures increased from 42.3% during 2002 to 2009 to 54.8% during 2010 to 2017 (P = 0.04). CONCLUSIONS: The prevalence of chromium allergy is decreasing. The EU Directive restricting the use of hexavalent chromium in leather goods is thought to be playing a central role in this change.

Prevalence of contact allergy in the general population: A systematic review and meta-analysis.

BACKGROUND: Contact allergy and allergic contact dermatitis are frequent conditions in the general population. OBJECTIVES: To provide an updated estimate of the prevalence of contact allergy in the general population based on data from our previous review combined with new data from an updated search for relevant studies published between 2007 and 2017. METHODS: Two authors independently searched PubMed for studies reporting on the prevalence of contact allergy in samples of the general population. Proportion meta-analyses were performed to calculate the pooled prevalence estimates of contact allergy. RESULTS: A total of 28 studies were included in the analysis, covering 20 107 patch tested individuals from the general population. Overall, the pooled prevalence of contact allergy was 20.1% (95% confidence interval [CI]: 16.8%-23.7%). In children and adolescents (<18 years), the prevalence was 16.5% (95%CI: 13.6%-19.7%). The prevalence was significantly higher in women (27.9% [95%CI: 21.7%-34.5%]) than in men (13.2% [95%CI: 9.3%-17.6%]). The most common allergen was nickel (11.4% [95%CI: 9.4%-13.5%]), followed by fragrance mix I (3.5% [95%CI: 2.1%-5.4%]), cobalt (2.7% [95%CI: 2.1%-3.4%]), Myroxylon pereirae (1.8% [95%CI: 1.0%-2.7%]), chromium (1.8% [95%CI: 1.3%-2.6%]), p-phenylenediamine (1.5% [95%CI: 1.0%-2.1%]), methylchloroisothiazolinone/methylisothiazolinone (1.5% [95%CI: 0.8%-2.5%]), and colophonium (1.3% [95%CI: 1.0%-1.6%]). CONCLUSIONS: This meta-analysis confirmed that at least 20% of the general population are contact-allergic to common environmental allergens. It highlights the need for more effective preventive strategies for common allergens in consumer goods, cosmetics, and the workplace.